Exam 2: Secondary Lymphoid Organs and Lymphocyte Trafficking Flashcards
What are the primary lymphoid organs?
- bone marrow (B and T cells originate)
2. thymus (t cells develop)
What are secondary lymphoid organs?
- lymph nodes (~500-600 in body)
- spleen
- MALT (mucosal-associated lymphoid tissue)
Lymphoid follicles are common within all____.
Secondary lymphoid organs
What type of lymphoid follicles are loose networks of follicular dendritic cells (FDC) and are rich in naive B cells or memory B cells?
Primary lymphoid follicles
“island of FDCs in a sea of B cells”
What type of lymphoid follicles are where germinal centers of replication and differentiation of B cells take places, after antigen stimulation?
Secondary lymphoid follicles
(recall) What type of cell are regular dendritic cells that present Ag to T cells and where are they made??
are WBCs made in bone marrow that migrate to tissues
Where are follicular dendritic cells present? What do they do?
in secondary lymphoid organs
catch and display antigen to B cells
How do follicular dendritic cells capture the antigen?
- complement protein and ABs bind to invaders and then the opsonized invader comes to secondary lymph organs
- here, FDCs have receptors that bind to complement proteins AND receptors that bind to Fc region of ABs
- FDCs attach to and hold opsonized Ags
What are the two types of receptors FDCs have that allow it to capture the antigen coming into the lymph organs?
- one that binds to complement proteins (Ex: C3a; opsonized on invader)
- one that binds to Fc region of ABs
What will clustering of FDCs on the BCRs (b cell receptors) cause a higher likelihood of?
the signal to the nucleus to activate
Once a B cell is activated, how fast and by what number do they proliferate?
number of B cells can double every six hours
The proliferating B cells push aside other B cells and create what?
a dark zone ( so many proliferating B cells makes it look dark)
Within the germinal centers, some B cells become what type of cells that will leave for bone marrow?
Plasma cells
What is somatic hypermutation (ass. with B cells becoming plasma cells in germinal centers)?
fine turns the Fab regions
Where are new mutations of somatic hypermutation of B cells tested in in the germinal center?
in the light zone
What happens to BCR B cells with lower affinity?
die by apoptosis and are eaten by macrophages
Where does class switching occur in the germinal center?
in the dark zone
depending on where we want the Ab to go “GAMED”
Which of the secondary lymphoid organs have follicles?
ALL of them: lymph nodes, spleen, and MALT
In secondary lymphoid organs, are naive T cells and naive B cells kept together?
no, they have separate areas
Once a T cell is activated in the secondary lymphoid organ, where will it migrate to?
to the B cell area to help activate B cells
How may an antigen enter the lymph nodes?
via blood OR lymph
How does the lymph enter a lymph node? How does the blood enter?
lymph enters at various points
blood enters through an arteriole
What are the two ways antigens can come in?
- in on APCs (dendritic cells)
or - arrive opsonized w/ ABs or complement (will be captured by FDCs)
From outside to inside what are the layers of the lymph node? Where is in each area?
- subcapsular or marginal sinus (lined w/ macrophages)
- Cortex (lymphiod follicles and B cell area)
- Paracortex (T cell area)
- Medullary sinus
- -> on to the next lymph node…
How may lymphocytes enter the lymph node?
via arteriole or via incoming lymph
What is the entry point for B and T cells to enter the secondary lymphoid organs from the blood?
High endothelial venule (HEV)
How many lymphocytes exit the blood and enter an average lymph node each second by passing b/w High Endothelial Cells?
about 10,000
How is the arrangement usually of endothelial cells in blood vessels?
usually OVERLAP like shingles and offer less room for passage of cells
(these are NOT HEVs)
How are High Endotheliam Venule cells in blood vessels arranged?
columnar and offer more room for passage of cells
What serves as the blood filter between an artery and vein where everything in the blood is allowed to enter?
the spleen
At rest, what percentage of cardiac output goes through the spleen?
5%
How long does it take the spleen to screen all the blood in the body?
30 minutes
T/F. The spleen receives many lymphatics.
False– NO lymphatics bringing lymph to the spleen
Where is blood entering the spleen diverted to? What cells are here?
diverted to marginal sinuses
- loaded with macrophages
- Dendrtic cells live here too
Where must blood ultimately filter back to from the spleen?
to the splenic vein
Where are the specific regions in the spleen where T cells and B cells hangout?
T cells–> area called periarteriolar lymphoid sheath (PALS)
B cells–> area b/w PALS and marginal sinuses
From outside in, list the “layers” of the spleen from where APC with Ag and opsonized Ag enter and what is contained in each.
- marginal sinus (lined with macrophages)
- B cell area (Lymphoid follicles and B cell area)
- PALS (T cell area)
- Splenic vein
–back to heart
What is the function of the spleen?
to remove old red blood cells and recycles iron
What does the spleen do hemoglobin?
it is broken down:
- globin into ind AAs
- heme into bilirubin (into pee or poop it goes)
What type of cell does the spleen hold large numbers of?
monocytes–> may migrate to battle sites to become macrophages or dendtritic cells
T/F. The spleen, just like the lymph nodes has HEVs.
False– the spleen has NO HEVs!
What are an example of Mucosal-Associated Lymphoid Tissue (MALT)?
Peyer’s Patches in ileum (GALT)
adults have about 200 of them
What are the Mucosal- associated lymphoid tissue (MALT) specifically called in the small intestine?
GALT (gut-associated lymphoid tissue)
where Peyer’s Patches are
Describe the anatomy of the Peyer’s Patches, what do they contain and don’t contain.
- High Endothelial venules (HEV) that allow lymphocytes to enter from blood)
- Outgoing lymphatics
- NO incoming lymphatics
T/F. Peyer’s Patches have incoming and outgoing lymphatics.
False–they DO NOT have incoming lymphatics, but they do have outgoing
How do antigens enter Peyer’s Patches?
M cells (microfold cells)
What do M cells (microfold cells) of the Peyer’s Pathes, lack that make them easily accessible for microorganisms in the intestine?
- lack villi
- lack mucus
How do M cells take in the Antigens and what antigens do they take in?
encloses intestinal antigens in vesicle (endosomes) and release contents into surrounding tissues surrounding the intestine
selective in what take in–> only take in what can bind to the molecules on the surface of M cells (lets things that would normally pass through the GI tract pass through)
Within Peyer’s Patches, what sites are antigens brought into and how to lymphocytes enter?
antigens are brought to distinct B cell and T cell areas
lymphocytes enter through HEVs
What two things do Peyer’s patches specialize in?
- specialize in making helper T cells that tell B cells to make IgA Abs
- specialize in making helper T cells that make Th2 cytokine profile
In Peyer’s Matches, describe from area where ADC w/ Ag or opsonized Ag enter and inward.
- Area where macrophages can eat it and present it (lined with macrophages)
- Area where FDC can catch and present to B cells (lymphoid follicles and B cell area)
- Area where T cells can be presented peptide Ags (T cell area)
- Lymph outflow to next secondary lymphoid tissue (activated B cells and T cells leaving)
Billions of T cells pass through secondary lymphoid organs, which become activated and what happens to those that dont?
very few become activated (those that meet their cognate Ag)
T cells that do not meet cognate Ag leave and continue to circulate
What do Naive T cells have many of?
How often do they circulate?
After how long of not meeting there Ag do they die of apoptosis?
have many adhesion molecules
circulate lymph/blood every 12-24 hours
do not meet cognate antigen after ~6 wks = apoptosis
What do Experienced T cells express?
certain adhesion molecules and expression of other adhesion molecules is now limited
What do the adhesion molecules that Experience T cells express depend on?
depend on where T cell was activated
Ex: Peyer’s Patch activation site = alpha4beta7 expression–> and T cells activated here will return to the gut
Do experience T cells have restricted travel? Where can they go?
yes; access to lymph organs where they were activated and access to site of infection
Describe B cell Trafficking.
- Billions of B cells pass through secondary lymphoid organs and only a small number will be activated (those that meet cognate Ag on FDCs)
- B cells that do not meet cognate Ag leave and continue to circualate
- Activated helper T cells in T cell areas proliferate and travel to germinal B cells areas activating B cells
Experienced B cells tend to settle down in bone morrow and make Abs (plasma cells)
Where do experienced B cells tend to settle down in?
bone marrow and make Abs (aka plasma cells)
